Skip to main content

Advertisement

SpringerLink
Log in

Is fibromyalgia a neurologic disease?

  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Fibromyalgia (FM) is characterized by abnormal pain sensitivity in response to diverse stimuli as well as persistent widespread pain and other symptoms such as fatigue and sleep disturbance. Progress has been made in identifying factors that contribute to the etiopathogenesis of abnormal pain sensitivity, but there is no single model of pathophysiology or treatment of FM that has gained wide acceptance among health care professionals.

We review the literature on the etiopathogenesis of abnormal pain sensitivity in FM and describe an explanatory model that serves as a source of testable hypotheses in our laboratory. This model posits that interactions of exogenous (eg, environmental stressors) and endogenous (eg, neuroendocrine dysfunction) abnormalities in genetically predisposed individuals lead to a final common pathway, ie, alterations in central nervous system function and neuropeptide production that underlie central sensitization and abnormal pain sensitivity. This model also suggests that efforts to develop and evaluate treatments for FM should focus on interventions with direct or indirect effects on central functions that influence pain sensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Yunus MB: Psychological aspects of fibromyalgia syndrome: a component of the dysfunctional spectrum syndrome. Baillieres Clin Rheumatol 1994, 8:811–837.

    Article  PubMed  CAS  Google Scholar 

  2. White KP, Speechley M, Harth M, Ostbye T: The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol 1999, 26:1570–1576. This is a well-designed, population-based study of the frequency of FM in London, Ontario, Canada. The ratio of women to men with FM was 9:1, a figure that is consistent with that of the Wolfe et al. study performed in Wichita, KS [3].

    PubMed  CAS  Google Scholar 

  3. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L: The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995, 38:19–28.

    Article  PubMed  CAS  Google Scholar 

  4. Pellegrino MJ, Waylonis GW, Sommer A: Familial occurrence of primary fibromyalgia. Arch Phys Med Rehabil 1989, 70:61–63.

    PubMed  CAS  Google Scholar 

  5. Buskila D, Neumann L, Hazanov I, Carmi R: Familial aggregation in the fibromyalgia syndrome. Semin Arthritis Rheum 1996, 26:605–611.

    Article  PubMed  CAS  Google Scholar 

  6. Buskila D, Neumann L: Fibromyalgia syndrome (FM) and nonarticular tenderness in relatives of patients with FM. J Rheumatol 1997, 24:941–944.

    PubMed  CAS  Google Scholar 

  7. Buskila D, Neumann L, Alhoashle A, Abu-Shakra M: Fibromyalgia syndrome in men. Semin Arthritis Rheum 2000, 30:47–51.

    Article  PubMed  CAS  Google Scholar 

  8. Yunus MB, Inanici F, Aldag JC, Mangold RF: Fibromyalgia in men: comparison of clinical features with women. J Rheumatol 2000, 27:485–490.

    PubMed  CAS  Google Scholar 

  9. Offenbaecher M, Bondy B, de Jonge S, et al.: Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region. Arthritis Rheum 1999, 42:2482–2488. This study identified a functional polymorphism in the regulatory region of the 5-HTT gene that is found more frequently in persons with FM than in healthy individuals. This functional polymorphism may contribute to abnormal blood serum levels of serotonin and to impaired pain inhibition associated with FM.

    Article  PubMed  CAS  Google Scholar 

  10. Bengtsson A, Henriksson KG, Larsson J: Muscle biopsy in primary fibromyalgia. Light-microscopical and histochemical findings. Scand J Rheumatol 1986, 15:1–6.

    PubMed  CAS  Google Scholar 

  11. Park JH, Phothimat P, Oates CT, et al.: Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Arthritis Rheum 1998, 41:406–413.

    Article  PubMed  CAS  Google Scholar 

  12. Bradley LA, Sotolongo A, Alberts KR, et al.: Abnormal regional cerebral blood flow in the caudate nucleus among fibromyalgia patients and non-patients is associated with insidious symptom onset. J Musculoskeletal Pain 1999, 7:285–292.

    Article  Google Scholar 

  13. Granges G, Littlejohn G: Pressure pain threshold in pain-free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. Arthritis Rheum 1993, 36:642–646.

    Article  PubMed  CAS  Google Scholar 

  14. Kosek E, Ekholm J, Hansson P: Increased pressure pain sensibility in fibromyalgia patients is located deep to the skin but not restricted to muscle tissue. Pain 1995, 63:335–339.

    Article  PubMed  CAS  Google Scholar 

  15. Wolfe F, Smythe HA, Yunus MB, et al.: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990, 33:160–172.

    Article  PubMed  CAS  Google Scholar 

  16. Arroyo JF, Cohen ML: Abnormal responses to electrocutaneous stimulation in fibromyalgia. J Rheumatol 1993, 20:1925–1931.

    PubMed  CAS  Google Scholar 

  17. Gibson SJ, Littlejohn GO, Gorman MM, et al.: Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome. Pain 1994, 58:185–193.

    Article  PubMed  CAS  Google Scholar 

  18. Staud R, Vierck CJ, Cannon RL, et al.: Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain 2001, 91:165–175. This is a well-designed study that documented enhanced pain sensitivity in response to repetitive thermal stimulation in patients with FM. These data contribute to the evidence that FM is associated with impairments in central pain inhibition function.

    Article  PubMed  CAS  Google Scholar 

  19. Kosek E, Hansson P: Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects. Pain 1997, 70:41–51.

    Article  PubMed  CAS  Google Scholar 

  20. Lautenbacher S, Rollman GB: Possible deficiencies of pain modulation in fibromyalgia. Clin J Pain 1997, 13:189–196.

    Article  PubMed  CAS  Google Scholar 

  21. Moldofsky H, Scarisbrick P, England R, Smythe H: Musculoskeletal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med 1975, 37:341–351.

    PubMed  CAS  Google Scholar 

  22. Lentz MJ, Landis CA, Rothermel J, Shaver JL: Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women. J Rheumatol 1999, 26:1586–1592.

    PubMed  CAS  Google Scholar 

  23. Carette S, Oakson G, Guimont C, Steriade M: Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia. Arthritis Rheum 1995, 38:1211–1217.

    Article  PubMed  CAS  Google Scholar 

  24. Moldofsky H, Lue FA, Smythe HA: Alpha EEG sleep and morning symptoms in rheumatoid arthritis. J Rheumatol 1983, 10:373–379.

    PubMed  CAS  Google Scholar 

  25. Moldofsky H, Saskin P, Lue FA: Sleep and symptoms in fibrositis syndrome after a febrile illness. J Rheumatol 1988, 15:1701–1704.

    PubMed  CAS  Google Scholar 

  26. Roizenblatt S, Moldofsky H, Benedito-Silva AA, Tufik S: Alpha sleep characteristics in fibromyalgia. Arthritis Rheum 2001, 44:222–230.

    Article  PubMed  CAS  Google Scholar 

  27. Affleck G, Urrows S, Tennen H, et al.: Sequential daily relations of sleep, pain intensity, and attention to pain among women with fibromyalgia. Pain 1996, 68:363–368.

    Article  PubMed  CAS  Google Scholar 

  28. McDermid AJ, Rollman GB, McCain GA: Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. Pain 1996, 66:133–144.

    Article  PubMed  CAS  Google Scholar 

  29. McCain GA, Tilbe KS: Diurnal hormone variation in fibromyalgia syndrome: a comparison with rheumatoid arthritis. J Rheumatol Suppl 1989, 19:154–157.

    PubMed  CAS  Google Scholar 

  30. Crofford LJ, Pillemer SR, Kalogeras KT, et al.: Hypothalamicpituitary-adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum 1994, 37:1583–1592.

    Article  PubMed  CAS  Google Scholar 

  31. Martinez-Lavin M, Hermosillo AG, Mendoza C, et al.: Orthostatic sympathetic derangement in subjects with fibromyalgia. J Rheumatol 1997, 24:714–718.

    PubMed  CAS  Google Scholar 

  32. Adler GK, Kinsley BT, Hurwitz S, et al.: Reduced hypothalamicpituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med 1999, 106:534–543.

    Article  PubMed  CAS  Google Scholar 

  33. Lariviere WR, Melzack R: The role of corticotropin-releasing factor in pain and analgesia. Pain 2000, 84:1–12.

    Article  PubMed  CAS  Google Scholar 

  34. Clauw DJ, Chrousos GP: Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation 1997, 4:134–153.

    PubMed  CAS  Google Scholar 

  35. Chrousos GP, Gold PW: The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992, 267:1244–1252.

    Article  PubMed  CAS  Google Scholar 

  36. Bennett RM, Cook DM, Clark SR, et al.: Hypothalamicpituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia. J Rheumatol 1997, 24:1384–1389.

    PubMed  CAS  Google Scholar 

  37. Bennett RM, Clark SR, Campbell SM, Burckhardt CS: Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain. Arthritis Rheum 1992, 35:1113–1116.

    Article  PubMed  CAS  Google Scholar 

  38. Bennett RM, Clark SC, Walczyk J: A randomized, doubleblind, placebo-controlled study of growth hormone in the treatment of fibromyalgia. Am J Med 1998, 104:227–231.

    Article  PubMed  CAS  Google Scholar 

  39. Duval P, Lenoir V, Moussaoui S, et al.: Substance P and neurokinin A variations throughout the rat estrous cycle: comparison with ovariectomized and male rats: II. Trigeminal nucleus and cervical spinal cord. J Neurosci Res 1996, 45:610–616.

    Article  PubMed  CAS  Google Scholar 

  40. Smith SS: Female sex steroid hormones: from receptors to networks to performance-actions on the sensorimotor system. Prog Neurobiol 1994, 44:55–86.

    Article  PubMed  CAS  Google Scholar 

  41. Anderberg UM, Liu Z, Berglund L, Nyberg F: Plasma levels on nociceptin in female fibromyalgia syndrome patients. Z Rheumatol 1998, 57(suppl 2):77–80.

    Article  PubMed  Google Scholar 

  42. Anderberg UM, Marteinsdottir I, Hallman J, Backstrom T: Variability in cyclicity affects pain and other symptoms in female fibromyalgia syndrome patients. J Musculoskeletal Pain 1998, 6:5–22.

    Article  Google Scholar 

  43. Krieger DT, Rizzo F: Serotonin mediation of circadian periodicity of plasma 17-hydroxycorticosteroids. Am J Physiol 1969, 217:1703–1707.

    PubMed  CAS  Google Scholar 

  44. Holmes MC, Di Renzo G, Beckford U, et al.: Role of serotonin in the control of secretion of corticotrophin releasing factor. J Endocrinol 1982, 93:151–160.

    Article  PubMed  CAS  Google Scholar 

  45. Russell IJ, Michalek JE, Vipraio GA, et al.: Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol 1992, 19:104–109.

    PubMed  CAS  Google Scholar 

  46. Wolfe F, Russell IJ, Vipraio G, et al.: Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol 1997, 24:555–559.

    PubMed  CAS  Google Scholar 

  47. Yunus MB, Dailey JW, Aldag JC, et al.: Plasma and urinary catecholamines in primary fibromyalgia: a controlled study. J Rheumatol 1992, 19:95–97.

    PubMed  CAS  Google Scholar 

  48. Giovengo SL, Russell IJ, Larson AA: Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia. J Rheumatol 1999, 26:1564–1569.

    PubMed  CAS  Google Scholar 

  49. Russell IJ, Orr MD, Littman B, et al.: Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994, 37:1593–1601.

    Article  PubMed  CAS  Google Scholar 

  50. Vaeroy H, Sakurada T, Forre O, et al.: Modulation of pain in fibromyalgia (fibrositis syndrome): cerebrospinal fluid (CSF) investigation of pain related neuropeptides with special reference to calcitonin gene related peptide (CGRP). J Rheumatol Suppl 1989, 19:94–97.

    PubMed  CAS  Google Scholar 

  51. Vaeroy H, Nyberg F, Terenius L: No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7. Pain 1991, 46:139–143.

    Article  PubMed  CAS  Google Scholar 

  52. Pillemer SR, Bradley LA, Crofford LJ, et al.: The neuroscience and endocrinology of fibromyalgia. Arthritis Rheum 1997, 40:1928–1939.

    Article  PubMed  CAS  Google Scholar 

  53. Graven-Nielsen T, Aspegren KS, Henriksson KG, et al.: Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain 2000, 85:483–491. This study demonstrates that ketamine, an NMDA antagonist, produces reductions in temporal summation and other measures of pain sensitivity in patients with FM.

    Article  PubMed  CAS  Google Scholar 

  54. Watkins LR, Milligan ED, Maier SF: Glial activation: a driving force for pathological pain. Trends Neurosci 2001, 24:450–455.

    Article  PubMed  CAS  Google Scholar 

  55. Peters ML, Vlaeyen JW, van Drunen C: Do fibromyalgia patients display hypervigilance for innocuous somatosensory stimuli? Application of a body scanning reaction time paradigm. Pain 2000, 86:283–292.

    Article  PubMed  CAS  Google Scholar 

  56. Alberts KR, Bradley LA, Alarcon GS, et al.: Anticipation of acute pain and high arousal feedback in women with fibromyalgia (FM), high pain anxiety, and high negative affectivity (NA) evokes increased pain and anterior cingulate cortex (ACC) activity without nociception. Arthritis Rheum 2000, 43:S173.

    Google Scholar 

  57. Missole C, Toroni F, Sigala S, et al.: Nerve growth factor in the anterior pituitary: localization in mammotroph cells and cosecretion with prolactin by a dopamine-regulated mechanism. Proc Natl Acad Sci U S A 1996, 93:4240–4245.

    Article  Google Scholar 

  58. Lindsay RM, Lockett C, Sternberg J, Winter J: Neuropeptide expression in cultures of adult sensory neurons: modulation of substance P and calcitonin gene-related peptide levels by nerve growth factor. Neuroscience 1989, 33:53–65.

    Article  PubMed  CAS  Google Scholar 

  59. Goebel MU, Mills PJ, Irwin MR, Ziegler MG: Interleukin-6 and tumor necrosis factor-alpha production after acute psychological stress, exercise, and infused isoproterenol: differential effects and pathways. Psychosom Med 2000, 62:591–598. This study is the first to demonstrate that a psychosocial stressor produces increased production of proinflammatory cytokines in healthy persons. This may mediate in part the increases in pain shown by patients with FM in response to stress.

    PubMed  CAS  Google Scholar 

  60. Davis MC,Zautra AJ, Reich JW: Vulnerability to stress among women in chronic pain from fibromyalgia and osteoarthritis.Ann Behav Med 2001, 23:215–226. This study is the first to demonstrate that patients with FM, compared to those with OA, show significantly greater increases in pain after exposure to a 30-minute psychosocial stressor.

    Article  PubMed  CAS  Google Scholar 

  61. Mountz JM, Bradley LA, Modell JG, et al.: Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum 1995, 38:926–938.

    Article  PubMed  CAS  Google Scholar 

  62. Saade NE, Kafrouni AI, Saab CY, et al.: Chronic thalamotomy increases pain-related behavior in rats. Pain 1999, 83:401–409.

    Article  PubMed  CAS  Google Scholar 

  63. Chudler EH, Sugiyama K, Dong WK: Nociceptive responses in the neostriatum and globus pallidus of the anesthetized rat. J Neurophysiol 1993, 69:1890–1903.

    PubMed  CAS  Google Scholar 

  64. Lineberry CG, Vierck CJ: Attenuation of pain reactivity by caudate nucleus stimulation in monkeys. Brain Res 1975, 98:119–134.

    Article  PubMed  CAS  Google Scholar 

  65. Kwiatek R, Barnden L, Tedman R, et al.: Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. Arthritis Rheum 2000, 43:2823–2833.

    Article  PubMed  CAS  Google Scholar 

  66. Coghill RC, Talbot JD, Evans AC, et al.: Distributed processing of pain and vibration by the human brain. J Neurosci 1994, 14:4095–4108.

    PubMed  CAS  Google Scholar 

  67. Coghill RC, Sang CN, Maisog JM, Iadarola MJ: Pain intensity processing within the human brain: a bilateral, distributed mechanism. J Neurophysiol 1999, 82:1934–1943.

    PubMed  CAS  Google Scholar 

  68. Cianfrini LR, McKendree-Smith NL, Bradley LA, et al.: Pain sensitivity and bilateral activation of brain structures during pressure stimulation of patients with fibromyalgia (FM) is not mediated by major depression (DEP). Arthritis Rheum 2001, 44:S395.

    Google Scholar 

  69. Kosek E, Ordeberg G: Abnormalities of somatosensory perception in patients with painful osteoarthritis normalize following successful treatment. Eur J Pain 2000, 4:229–238.

    Article  PubMed  CAS  Google Scholar 

  70. Bajaj P, Bajaj P, Graven-Nielsen T, Arendt-Nielsen L: Osteoarthritis and its association with muscle hyperalgesia: an experimental controlled study. Pain 2001, 93:107–114.

    Article  PubMed  CAS  Google Scholar 

  71. Iadarola MJ, Max MB, Berman KF, et al.: Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain 1995, 63:55–64.

    Article  PubMed  CAS  Google Scholar 

  72. Di Piero V, Jones AK, Iannotti F, et al.: Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy. Pain 1991, 46:9–12.

    Article  Google Scholar 

  73. Petrovic P, Ingvar M, Stone-Elander S, et al.: A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy. Pain 1999, 83:459–470.

    Article  PubMed  CAS  Google Scholar 

  74. Pauli P, Wiedemann G, Nickola M: Pain sensitivity, cerebral laterality, and negative affect. Pain 1999, 80:359–364.

    Article  PubMed  CAS  Google Scholar 

  75. Weigent DA, Bradley LA, Blalock JE, Alarcon GS: Current concepts in the pathophysiology of abnormal pain perception in fibromyalgia. Am J Med Sci 1998, 315:405–412.

    Article  PubMed  CAS  Google Scholar 

  76. Hudson JI, Hudson MS, Pliner LF, et al.: Fibromyalgia and major affective disorder: a controlled phenomenology and family history study. Am J Psychiatry 1985, 142:441–446.

    PubMed  CAS  Google Scholar 

  77. Hudson JI, Goldenberg DL, Pope HG Jr, et al.: Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med 1992, 92:363–367.

    Article  PubMed  CAS  Google Scholar 

  78. Hudson JI, Pope HG Jr: Fibromyalgia and psychopathology: is fibromyalgia a form of “affective spectrum disorder”? J Rheumatol Suppl 1989, 19:15–22.

    PubMed  CAS  Google Scholar 

  79. Aaron LA, Bradley LA, Alarcon GS, et al.: Psychiatric diagnoses in patients with fibromyalgia are related to health careseeking behavior rather than to illness. Arthritis Rheum 1996, 39:436–445.

    Article  PubMed  CAS  Google Scholar 

  80. Kersh BC, Bradley LA, Alarcon GS, et al.: Psychosocial and health status variables independently predict health care seeking in fibromyalgia. Arthritis Rheum 2001, 45:362–371.

    Article  PubMed  CAS  Google Scholar 

  81. Aaron LA, Bradley LA, Alarcon GS, et al.: Perceived physical and emotional trauma as precipitating events in fibromyalgia. Associations with health care seeking and disability status but not pain severity. Arthritis Rheum 1997, 40:453–460.

    Article  PubMed  CAS  Google Scholar 

  82. Rainville P, Duncan GH, Price DD, et al.: Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 1997, 277:968–971.

    Article  PubMed  CAS  Google Scholar 

  83. Melzack R: Gate control theory: on the evolution of pain concepts. Pain Forum 1996, 5:125–128.

    Google Scholar 

  84. Bradley LA, Alarcon GS: Fibromyalgia. In Arthritis and Allied Conditions, vol. 2. Edited by Koopman WJ. Baltimore, MD: Lippincott Williams & Wilkins; 2001:1811–1844.

    Google Scholar 

  85. Bradley LA, Alberts KR: Psychological and behavioral approaches to pain management for patients with rheumatic disease. Rheum Dis Clin North Am 1999, 25:215–232.

    Article  PubMed  CAS  Google Scholar 

  86. Nezu AM, Nezu CM, Lombardo ER: Cognitive-behavior therapy for medically unexplained symptoms: a critical review of the treatment literature. Behav Ther 2001, 32:537–583.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Alabama at Birmingham, Division of Clinical Immunology and Rheumatology, 475 Boshell Diabetes Building, 1808 7th Avenue South, 35294, Birmingham, AL, USA

    Laurence A. Bradley PhD, Nancy L. McKendree-Smith PhD, Graciela S. Alarcón MD, MPH & Leanne R. Cianfrini MA

Authors
  1. Laurence A. Bradley PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nancy L. McKendree-Smith PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graciela S. Alarcón MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leanne R. Cianfrini MA
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bradley, L.A., McKendree-Smith, N.L., Alarcón, G.S. et al. Is fibromyalgia a neurologic disease?. Current Science Inc 6, 106–114 (2002). https://doi.org/10.1007/s11916-002-0006-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-002-0006-9

Keywords

Search

Navigation